Uptake of organic anions by the liver has kinetic characteristics of facilitated diffusion. Although a carrier or receptor for organic anions has been postulated to be present on the plasma membrane of the hepatocyte, it has not been demonstrated directly. In the search for the putative organic anion receptor, the interaction of sulfobromophthalein (BSP) with "sinusiodal" and "canalicular" rat liver cell plasma membrane (LPM) subfractions has been studied. High affinity, saturable binding, which was eliminated by trypsin preincubation, has been demonstrated using a filtration assay. By means of photoactivation of 3S-BSP, binding of ligand to the "sinusoidal" LPM subfraction was localized to a 55,000 dalton protein, and this protein was purified from LPM by affinity chromatography on BSP-GSH-agarose gel. Although this isolated protein binds bilirubin with high affinity, its potential role in transport remains under investigation. Two rat models (regeneration and fasting) in which the influx rate of organic anions is reduced, have been characterized by kinetic analysis of multiple indicator dilution studies performed in isolated perfused liver. Study of the interaction of 35S-BSP to LPM from these may reveal changes in ligand-protein interaction. The aims of future studies are to (1) characterize interaction of 35S-BSP to the "canalicular" LPM subfraction; (2) prepare antibody to the "sinusoidal" binding protein and study its effects on binding and transport in vivo and in vitro; and (3) study the interaction of organic anions with LPM from fasted and regenerating livers.